Abstract
AB014. The accurate classification of high-grade glioma, IDH-wildtype, is based on methylation profiling: a case report
Shigeki Takada1, Yasuhide Takeuchi2, Yasuhide Makino1, Etsuko Yamamoto1, Noritaka Sano1, Masahiro Tanji1, Yohei Mineharu1, Yoshiki Arakawa1
1Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan;
2Department of Diagnostic Pathology, Kyoto University Graduate School of Medicine, Kyoto, Japan
Correspondence to: Yoshiki Arakawa, MD, PhD. Department of Neurosurgery, Kyoto University Graduate School of Medicine, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. Email: yarakawa@kuhp.kyoto-u.ac.jp.
Background: The 2021 World Health Organization (WHO) classification has significantly enhanced the molecular diagnostics of diffuse gliomas, emphasizing the role of molecular features alongside histology. However, accurate classification remains challenging, particularly for high-grade gliomas, IDH-wildtype. DNA methylation profiling provides an unbiased diagnostic approach, offering valuable insights into tumor classification. Here, we present a case of a high-grade glioma, initially diagnosed as glioblastoma, IDH-wildtype based on histological and genetic analysis, but later reclassified as a diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype (RTK2 subtype) through methylation profiling.
Case Description: A 7-year-old boy presenting with seizures was admitted to our hospital, where brain magnetic resonance imaging revealed a tumor in the right temporal lobe. Intraoperative histology indicated a high-grade glioma, prompting maximal resection. Diagnosis according to the 2021 WHO classification involved histological analysis, immunohistochemistry, testing for specific genetic alterations, and DNA methylation profiling. Histological and immunohistochemical assessment initially identified the tumor as a high-grade astrocytoma, IDH-wildtype. Specific genetic testing revealed IDH1-wildtype, IDH2-wildtype, and TERT promoter mutation, consistent with a diagnosis of glioblastoma, IDH-wildtype. However, methylation profiling yielded a classifier score of 0.99 for a diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype (RTK2 subtype).
Conclusions: Our case illustrated that conventional histological and genetic analysis classification can be reclassified according to the DNA methylation analysis, demonstrating that methylation profiling is useful to accurately classify high-grade gliomas, particularly those of the IDH-wildtype subtype.
Keywords: High-grade glioma; IDH-wildtype; methylation profiling; case report
Acknowledgments
Funding: None.
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://cco.amegroups.com/article/view/10.21037/cco-24-ab014/coif). Y.A. reported grants from Philips, Otsuka, Chugai, Nihon Medi-Physic, Daiichi Sankyo, Stryker, Eisai, Japan Blood Products Organization, Ono Pharmaceutical, Taiho Pharma, Sumitomo Dainippon Pharma, Astellas Pharma, Sanofi; personal fees from Nippon Kayaku, Novocure, UCB Japan, Ono Pharmaceutical, Brainlab, Merck, Chugai, Eisai, Daiichi Sankyo, Carl Zeiss, and Nihon Medi-Physic outside the submitted work. The other authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committees and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the noncommercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
Cite this abstract as: Takada S, Takeuchi Y, Makino Y, Yamamoto E, Sano N, Tanji M, Mineharu Y, Arakawa Y. AB014. The accurate classification of high-grade glioma, IDH-wildtype, is based on methylation profiling: a case report. Chin Clin Oncol 2024;13(Suppl 1):AB014. doi: 10.21037/cco-24-ab014
